EGF receptor

EGF receptor
	Scheme drawing. The exact structure has not yet been fully clarified.
	Existing structural data : Ectodomain : 1IVO , 1MOX , 1NQL , 1YY9 , 3B2U , 3B2V , 3C09 ; Juxtamembrane Domain: 1Z9I (NMR); Tyrosine kinase: 1M14 , 1M17 , 1XKK , 2EB2 , 2EB3 , 2GS2 , 2GS6 , 2GS7 , 2ITN , 2ITO , 2ITP , 2ITQ , 2ITT , 2ITU , 2ITV , 2ITW , 2ITX , 2ITY , 2ITZ , 2J5E , 2J5F , 2J6M , 2JIT , 2JIU , 2JIV , 2RF9 , 2RFD , 2RFE , 2RGP , 3BEL , 3BUO , 3GOP , 3GT8
Properties of human protein
Mass / length primary structure	1186 amino acids (monomer)
Secondary to quaternary structure	single-pass membrane receptor, dimer
Isoforms	4th
Identifier
Gene name	EGFR
External IDs	OMIM : 131550 ; UniProt : P00533 ;
Enzyme classification
EC, category	2.7.10.1 , tyrosine kinase
Response type	Phosphorylation
Substrate	ATP + protein L-tyrosine
Products	ADP + protein L-tyrosine phosphate
Occurrence
Parent taxon	Vertebrates
	Orthologue

The EGF receptor (Abbreviation for E pidermal G rowth F actor R preceptor , EGFR ) is a protein in the cell membranes of vertebrates ; it is the receptor for the E pidermal- G rowth- F actor (EGF) and is a member of the ErbB family, a subfamily of four closely related receptor tyrosine kinases : EGFR1 / HER1 (ErbB-1), HER2 / c-neu ( ErbB-2 ), HER3 (ErbB-3) and HER4 (ErbB-4).

properties

The EGF receptor is a transmembrane receptor with intrinsic tyrosine kinase activity. The receptor has only one membrane passage and the cytoplasmic portion a kinase - domain with ATP-binding site. The activation ( dimerization ) of EGFR takes place through extracellular binding of the ligands Epidermal Growth Factor (EGF) and Transforming Growth Factor (TGFα), whose signal it transmits into the cell interior via autophosphorylation and the recruitment of signal molecules such as Akt / PKB , MEK or STAT protein ( Signal transduction ), which ultimately stimulate cell growth and prevent apoptotic (programmed) cell death. The EGF receptor is thus one of the receptors for growth factors .

1,25 (OH) ₂ D ₃ inhibits this receptor- ligand complex, which possibly contributes to the effectiveness of vitamin D in psoriasis treatment, because psoriatic cells produce more TGFα.

Cancer therapy

The EGF receptor is upregulated in various types of tumors and / or found in mutated form, which leads to the fact that the tumor cells grow and multiply in an uncontrolled manner. This can lead to increased metastasis . There is also a lower sensitivity to chemotherapy and radiotherapy .

Novel cancer therapies aim to block this oncogenic signal from EGFR and thus prevent tumor growth. Already successfully tested and approved substances these so-called targeted cancer therapy (Engl. Targeted therapy ) include gefitinib ( Iressa ), erlotinib ( Tarceva ) and afatinib ( Giotrif ), or the monoclonal antibody cetuximab ( Erbitux ) and panitumumab ( Vectibix ).

The Liquid Biopsy can complement the diagnosis of tumors under certain conditions, for example when a primary tumor is found, the non-small cell lung cancer ( English non small cell lung cancer , NSCLC). Here the liquid biopsy takes place to detect an EGFR- T790M mutation. The EGFR mutation replaces a threonine (T) with a methionine (M) at position 790 of exon 20.

Protein structure

The structure of the EGFR monomer consists of:

the ectodomain ( extracellular domain ) with two homologous domains I (L1) and III (L2) and the cysteine-rich domains II (CR1 or S1) and IV (CR2 or S2)
a single-pass transmembrane α-helix
the catalytic region in the cytoplasm with the tyrosine kinase flanked by the juxtamembrane and C-terminal regulatory region.

So far the overall structure of the dimer is unknown, but essential parts have already been determined: domains I-III and a few residues of domain IV ( single crystal ), the juxtamembrane region alone ( NMR ) or together with the tyrosine kinase (single crystal) and also the tyrosine kinase alone (Single crystal).

literature

K. Oda, Y. Matsuoka, A. Funahashi, H. Kitano: A comprehensive pathway map of epidermal growth factor receptor signaling. In: Molecular systems biology. Volume 1, 2005, S. 2005.0010, doi : 10.1038 / msb4100014 , PMID 16729045 , PMC 1681468 (free full text).
PR Dutta, A. Maity: Cellular responses to EGFR inhibitors and their relevance to cancer therapy. In: Cancer letters. Volume 254, Number 2, September 2007, pp. 165-177, doi : 10.1016 / j.canlet.2007.02.006 , PMID 17367921 , PMC 1986742 (free full text) (review).

Web links

Somatic Mutations in Epidermal Growth Factor Receptor DataBase

Individual evidence

↑ F. Ciardiello et al: EGF receptor blockade with monoclonal antibodies and so-called "small molecules". In: Onkologie - International Journal for Cancer Research and Treatment. Vol. 28 (suppl 4), 2005, pp. 18-24.

↑ D. Ayeni, K. Politi, SB Goldberg: Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer. In: Clinical Cancer Research . Volume 21, number 17, September 2015, pp. 3818-3820, doi : 10.1158 / 1078-0432.CCR-15-1211 , PMID 26169963 , PMC 4720502 (free full text).

[1] F. Ciardiello et al: EGF receptor blockade with monoclonal antibodies and so-called "small molecules". In: Onkologie - International Journal for Cancer Research and Treatment. Vol. 28 (suppl 4), 2005, pp. 18-24.

[2] D. Ayeni, K. Politi, SB Goldberg: Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer. In: Clinical Cancer Research . Volume 21, number 17, September 2015, pp. 3818-3820, doi : 10.1158 / 1078-0432.CCR-15-1211 , PMID 26169963 , PMC 4720502 (free full text).